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Effect of subinhibitory concentrations of antimicrobials on meningococcal adherence
Abstract:
Meningococci adhere to human pharyngeal cells and agglutinate erythrocytes. These events are dependent upon pili and are reduced by encapsulation. The effect of subinhibitory concentrations of seven antimicrobials on meningococcal adherence, antimicrobials on meningococcal adherence, piliation, hemagglutination (HA), and bacterial proteins was studied to determine their potential for modifying virulence. Piliation was reduced by most antibiotics but was most markedly (greater than 70%) reduced by rifampin, tobramycin, and VCN (vancomycin, colistin, and nystatin). Bacterial proteins as determined by sodium dodecyl sulphate--polyacrylamide gel electrophoresis were altered: tetracycline, sulfamethoxazole, rifampin, and VCN caused loss of a 43-45 K protein and a general decrease in all stainable protein bands, while erythromycin, ampicillin, and tobramycin only caused an increase in a 28 K protein. HA was reduced by ampicillin, tobramycin, erythromycin, and VCN but interstrain variability was present. Epithelial cell adherence was diminished by an average of 45% compared to controls. The meningococcal strains lost HA, piliation, and adherence in the same rank order, however, there was no significant rank correlation of antibiotic inhibitory activities on these parameters. These results indicate that subinhibitory antibiotic concentrations reduce meningococcal piliation and alter other bacterial proteins; these changes are associated with diminished adherence and hemagglutination, alterations which may be markers of meningococcal virulence.
Insights
Subinhibitory antibiotic concentrations reduce meningococcal virulence factors like piliation and alter bacterial proteins. These changes lead to decreased adherence and hemagglutination, potentially marking reduced virulence.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Neisseria meningitidis (meningococci) adhere to human pharyngeal cells and agglutinate erythrocytes, processes crucial for infection.
- These virulence factors, including pili and hemagglutination (HA), are known to be reduced by encapsulation.
Purpose of the Study:
- To investigate the effects of subinhibitory concentrations of seven antimicrobials on meningococcal virulence.
- To determine if these antimicrobial-induced changes in piliation, hemagglutination, and bacterial proteins correlate with altered adherence and potential virulence modification.
Main Methods:
- Assessed the impact of subinhibitory antimicrobial concentrations on meningococcal piliation, hemagglutination (HA), bacterial protein profiles (using SDS-PAGE), and adherence to human pharyngeal cells.
- Evaluated seven different antimicrobials, including rifampin, tobramycin, vancomycin, colistin, nystatin, tetracycline, sulfamethoxazole, erythromycin, and ampicillin.
Main Results:
- Most antibiotics reduced piliation, with rifampin, tobramycin, and vancomycin, colistin, and nystatin (VCN) showing the most significant reduction (>70%).
- Antimicrobials altered bacterial protein profiles, with some causing loss of specific proteins and others increasing a 28 K protein.
- Subinhibitory antibiotic concentrations diminished epithelial cell adherence by an average of 45% and reduced hemagglutination, though interstrain variability was noted.
Conclusions:
- Subinhibitory antibiotic concentrations can significantly reduce meningococcal piliation and alter bacterial protein expression.
- These alterations are associated with diminished bacterial adherence and hemagglutination, suggesting a potential mechanism for reducing meningococcal virulence.